HS is a key antisecretory molecule against cholera toxin-induced diarrhoea in mice: Evidence for non-involvement of the AC/cAMP/PKA pathway and AMPK.

Hydrogen sulphide (HS) is a gasotransmitter that participates in various physiological and pathophysiological processes within the gastrointestinal tract. We studied the effects and possible mechanism of action of HS in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of HS were investigated using an intestinal fluid secretion model in isolated intestinal loops on anaesthetized mice treated with CT. NaHS and Lawesson's reagent and l-cysteine showed antisecretory activity through reduction of intestinal fluid secretion and loss of Cl induced by CT. Pretreatment with an inhibitor of cystathionine-γ-lyase (CSE), dl-propargylglycine (PAG), reversed the effect of l-cysteine and caused severe intestinal secretion. Co-treatment with PAG and a submaximal dose of CT increased intestinal fluid secretion, thus supporting the role of HS in the pathophysiology of cholera. CT increased the expression of CSE and the production of HS. Pretreatment with PAG did not reverse the effect of SQ 22536 (an AC inhibitor), bupivacaine (inhibitor of cAMP production), KT-5720 (a PKA inhibitor), and AICAR (an AMPK activator). The treatment with Forskolin does not reverse the effects of the HS donors. Co-treatment with either NaHS or Lawesson's reagent and dorsomorphin (an AMPK inhibitor) did not reverse the effect of the HS donors. HS has antisecretory activity and is an essential molecule for protection against the intestinal secretion induced by CT. Thus, HS donor drugs are promising candidates for cholera therapy. However, more studies are needed to elucidate the possible mechanism of action.